Induction of tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) as early growth responses in rat hepatocytes in primary culture.

Early growth response with respect to tissue-type plasminogen activator (tPA) and type-1 plasminogen activator inhibitor (PAI-1) gene expression was studied in rat hepatocytes in primary culture. The genes for tPA and PAI-1 could be categorized as a delayed early growth response (DER) gene and an immediate early growth response (IER) gene, respectively. The expression of tPA was much higher in growth-promoting than in static culture conditions (i.e., cultured at low density and/or on a collagen-coated dish), and that of PAI-1 was regulated in the opposite direction. Experiments using dibutyryl cAMP (dbcAMP) and H-89 showed that the cAMP/A-kinase system might be involved in the induction of the early growth response of tPA and in the augmentation of PAI-1 mRNA induction by dbcAMP. These fibrinolytic components, whose expression is closely associated with hepatocyte growth, may play important roles in pathophysiological events in the liver such as liver regeneration.